Laboratory Sciences and Services Division icddr,b Dhaka Bangladesh.
Graduate School of Medicine Department of Neuroscience Nagoya University Nagoya Japan.
Ann Clin Transl Neurol. 2019 Mar 3;6(4):708-715. doi: 10.1002/acn3.744. eCollection 2019 Apr.
TLR4 plays an important role in the pathogenesis of Guillain-Barré syndrome (GBS). The relationships between polymorphisms and susceptibility to GBS are poorly understood. We investigated the frequency and assessed the association of two single nucleotide polymorphisms (SNPs) in the extracellular domain of (Asp299Gly and Thr399Ile) with disease susceptibility and the clinical features of GBS in a Bangladeshi cohort.
A total of 290 subjects were included in this study: 141 patients with GBS and 149 unrelated healthy controls. The polymorphisms Asp299Gly and Thr399Ile were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.
The minor 299Gly allele was significantly associated with GBS susceptibility (=0.0137, OR = 1.97, 95% CI = 1.17-3.31), and was present at a significantly higher frequency in patients with the acute motor axonal neuropathy (AMAN) subtype of GBS (=0.0120, OR = 2.37, 95% CI = 1.26-4.47) than acute inflammatory demyelinating polyneuropathy (AIDP) subtype (=0.961, OR = 1.15, 95% CI = 0.38-3.48); when compared to healthy controls. The genotype frequency of the Asp299Gly polymorphism was not significantly different between patients with GBS and healthy controls. The Asp299-Thr399 haplotype was associated with a significantly lower risk of developing GBS (=0.0451, OR = 0.63, 95% CI = 0.40-0.99). No association was observed between the Thr399Ile polymorphism and GBS disease susceptibility.
The minor 299Gly allele was associated with increased susceptibility to GBS and the axonal GBS subtype in the Bangladeshi population. However, no associations were observed between the genotypes of the Asp299Gly and Thr399Ile SNPs and antecedent infection or disease severity in Bangladeshi patients with GBS.
TLR4 在吉兰-巴雷综合征（GBS）的发病机制中发挥重要作用。然而，多态性与 GBS 易感性之间的关系尚未得到充分了解。我们研究了孟加拉国队列中 TLR4 外显子中的两个单核苷酸多态性（SNP）（Asp299Gly 和 Thr399Ile）的频率，并评估了它们与 GBS 疾病易感性和临床特征的关联。
本研究共纳入 290 例受试者：141 例 GBS 患者和 149 例无关健康对照者。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测 TLR4 多态性 Asp299Gly 和 Thr399Ile 的基因型。
TLR4 等位基因 299Gly 较少见，与 GBS 易感性显著相关（=0.0137，OR=1.97，95%CI=1.17-3.31），且在急性运动轴索性神经病（AMAN）型 GBS 患者中出现频率明显更高（=0.0120，OR=2.37，95%CI=1.26-4.47），而非急性炎症性脱髓鞘性多发性神经病（AIDP）型 GBS（=0.961，OR=1.15，95%CI=0.38-3.48）；与健康对照组相比。GBS 患者与健康对照组之间 TLR4 多态性 Asp299Gly 基因型频率无显著差异。Asp299-Thr399 单倍型与 GBS 发病风险显著降低相关（=0.0451，OR=0.63，95%CI=0.40-0.99）。Thr399Ile 多态性与 GBS 易感性无关。
孟加拉国人群中，TLR4 等位基因 299Gly 较少见与 GBS 易感性增加及轴索性 GBS 亚型相关。然而，孟加拉国 GBS 患者中，Asp299Gly 和 Thr399Ile SNP 基因型与前驱感染或疾病严重程度之间未见关联。
